Microfluidics technology has grown explosively over the last decade for the potential to carry out certain chemical, physical or biotechnological processing techniques. Microfluidics refers to the manipulation of minute quantities of fluid, typically in the micro- to nano-liter range. The use of planar fluidic devices for performing small-volume chemistry was first proposed by analytical chemists, who used the term “miniaturized total chemical analysis systems” (μTAS) for this concept. An increasing number of researchers from many disciplines other than analytical chemistry have embraced the fundamental fluidic principle of μTAS as a way of developing new research tools for chemical and biological applications. To reflect this expanded scope, the broader terms “microfluidics” and “Lab-on-a-chip (LOC)” are now often used in addition to μTAS.
The first generation microfluidic technologies are based on the manipulation of continuous liquid flow through microfabricated channels. Actuation of liquid flow is implemented either by external pressure sources, integrated mechanical micropumps, or by electrokinetic mechanisms. Continuous-flow systems are adequate for many well-defined and simple biochemical applications, but they are unsuitable for more complex tasks requiring a high degree of flexibility or complicated fluid manipulations. Droplet based microfluidics is an alternative to the continuous-flow systems, where the liquid is divided into discrete independently controllable droplets, and these droplets can be manipulated to move in channels or on a substrate. By using discrete unit-volume droplets, a microfluidic function can be reduced to a set of repeated basic operations, i.e., moving one unit of fluid over one unit of instance. A number of methods for manipulating microfluidic droplets have been proposed in the literature. These techniques can be classified as chemical, thermal, acoustical, and electrical methods. Among all methods, electrical methods to actuate droplets have received considerable attention in recent years.
In droplet-based microfluidic devices, a liquid is sandwiched between two parallel plates and transported in the form of droplets. Droplet-based microfluidic systems offer many advantages: they have low power consumption and require no mechanical components such as pumps or valves. In recent years, droplet-based microfluidic systems have been broadly utilized in applications such as the mixing of analytes and reagents, the analysis of biomolecules, and particle manipulation. In digital microfluidic systems, electro-wetting-on-dielectric (EWOD) and liquid dielectrophoresis (LDEP) are the two main mechanisms that are used to dispense and manipulate droplets. EWOD and LDEP both exploit electromechanical forces to control the droplet. EWOD microsystems are usually utilized to create, transport, cut, and merge liquid droplets. In these systems, the droplet is sandwiched between two parallel plates and actuated under the wettability differences between the actuated and nonactuated electrodes. In LDEP microsystems, the droplet is placed on coplanar electrodes. When a voltage is applied, the liquids become polarizable and flow toward regions of stronger electric field intensity. The differences between LDEP and EWOD actuation mechanisms are the actuation voltage and the frequency. In EWOD actuation, DC or low-frequency AC voltage, typically <100 V, is applied, whereas LDEP needs higher actuation voltage (200-300 Vrms) and higher frequency (50-200 kHz).
Electrowetting-on-dielectric (EWOD) is one of the most common electrical methods. Digital microfluidics such as the Lab-on-a-chip (LOC) generally means the manipulation of droplets using EWOD technique. The conventional EWOD based LOC device generally includes two parallel glass plates. The bottom plate contains a patterned array of individually controllable electrodes, and the top plate is coated with a continuous ground electrode. Electrodes are preferably formed by a material like indium tin oxide (ITO) that have the combined features of electrical conductivity and optical transparency in thin layer. A dielectric insulator coated with a hydrophobic film is added to the plates to decrease the wettability of the surface and to add capacitance between the droplet and the control electrode. The droplet containing biochemical samples and the filler medium are sandwiched between the plates while the droplets travel inside the filler medium. In order to move a droplet, a control voltage is applied to an electrode adjacent to the droplet and at the same time the electrode just under the droplet is deactivated.
In recent years, LDEP has also attracted considerable interest because it is easily implemented and it can dispense and manipulate tiny droplets, ranging from nanoliters to picoliters. Liquid DEP actuation is defined as the attraction of polarizable liquid masses into the regions of higher electric-field intensity. The basic structure of the liquid DEP droplet dispenser consists of two coplanar electrodes coated with a dielectric layer to protect them from electrolysis. Ahmed and Jones optimized liquid DEP droplet dispensing and created a picoliter droplet on coplanar electrodes. The effects of surface coatings and critical factors on the reliable actuation of the liquid DEP using coplanar electrodes have been reported. Fan et al. transformed coplanar LDEP electrodes into two parallel LDEP electrodes. The parallel structure of LDEP devices was employed for a micromixer and integrated with an EWOD microsystem. Transporting, splitting, and merging dielectric droplets are achieved by DEP in a parallel-plate (bi-planar) device, which expands the fluids of digital microfluidics from merely being conductive and aqueous to being non-conductive. Bi-planar DEP actuation of dielectric droplets is achieved by applying voltage between parallel electrodes, a liquid dielectric droplet of a higher relative permittivity is pumped by DEP into the region of a lower relative permittivity (e.g., air).
Unfortunately, the conventional LOC systems employing EWOD technique built to date are still highly specialized to particular applications. The current LOC systems rely heavily on the manual manipulation and optimization of the bioassays. Moreover, current applications and functions in the LOC system are time-consuming and require costly hardware design, testing and maintenance procedures. The biggest disadvantage about these systems is the “hardwired” electrodes. “Hardwired” means the shapes, the sizes, locations, and the electrical wiring traces to the controller of the electrodes are physically confined to permanently etched structures. Regardless of their functions, once the electrodes are fabricated, their shapes, sizes, locations and traces can't be changed. So this means high non-recurring engineering costs relative to LOC designs and the limited ability to update the functionality after shipping or partial re-configuration of the portion of the LOC.
There is a need in the art for a system and method for reducing the labor and cost associated with generating the microfluidic systems with the droplet manipulation. The art raises the LOC designs to the application level to relieve LOC designers from the burden of manual optimization of bioassays, time consuming hardware design, costly testing and maintenance procedures.
There is a need in the art for a system and method for reducing the labor and cost associated with generating the microfluidic systems with the droplet manipulation. Microelectrode array architecture technique can provide the field-programmability that the electrodes and the overall layout of the LOC can be software programmable. A microfluidic device or embedded system is said to be field-programmable or in-place programmable if its firmware (stored in non-volatile memory, such as ROM) can be modified “in the field,” without disassembling the device or returning it to its manufacturer. This is often an extremely desirable feature, as it can reduce the cost and turnaround time for replacement of buggy or obsolete firmware. The ability to update the functionality after shipping, partial re-configuration of the portion of the design and the low non-recurring engineering costs relative to an LOC design offer advantages for many applications.
Also, based on the novel Microelectrode Array Architecture, the art to manipulate droplets in LOC systems can be dramatically improved. There are various embodiments of present invention in the advanced manipulations of droplets in creating, transportation, mixing and cutting based on the EWOD Microelectrode Array Architecture.
It is believed that a Field-Programmable Lab-on-chip (FPLOC) employing the Microelectrode Array Architecture can provide a number of advantages over the conventional digital fluidic system due to its ability of programming a new LOC system dynamically based on field applications. The field-programmability can dramatically improve the turn-around time of the LOC designs and it also raises the LOC designs to the applications level to relieve LOC designers from the burden of manual optimization of bioassays, time consuming hardware design, costly testing and maintenance procedures.